ABSTRACT
Chemical investigation of the culture extract of an endophytic Penicillium citrinum from Dendrobium officinale, afforded nine citrinin derivatives (1-9) and one peptide-polyketide hybrid GKK1032B (10). The structures of these compounds were determined by spectroscopic methods. The absolute configurations of 1 and 2 were determined for the first time by calculation of electronic circular dichroism (ECD) data. Among them, GKK1032B (10) showed significant cytotoxicity against human osteosarcoma cell line MG63 with an IC50 value of 3.49 μmol·L-1, and a primary mechanistic study revealed that it induced the apoptosis of MG63 cellsvia caspase pathway activation.
Subject(s)
Humans , Apoptosis , Bone Neoplasms , Caspases , Osteosarcoma/drug therapy , PenicilliumABSTRACT
Objective To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission. Methods The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis. Results A total of 244 imported malaria cases were reported in Jiangsu Province in 2019, and the time to initial diagnosis of the cases were 1-12 days, with mean time of (1.53 ± 1.65) days, with median time of one day. The highest number of malaria cases seeking healthcare services were found on the day of developing primary symptoms (76 cases, 31.1%), followed by on the second day (68 cases, 27.9%), on the third day (46 cases, 18.9%), and 54 cases (22.1%) received initial diagnosis 3 days following presence of primary symptoms, including 3 cases with initial diagnosis at more than one week. High proportions of imported malaria cases with a delay in the time to initial diagnosis were seen in migrant workers who returned to China in January (14 cases, 5.7%) and December (13 cases, 5.3%) and those aged between 41 and 50 years (32 cases, 13.1%). Multivariate logistic regression analysis showed relative short time to initial diagnosis among imported malaria cases returning to China on March [odds ratio (OR) = 0.16, P = 0.03, 95% confidence interval (CI): (0.03, 0.85)] and those with a history of overseas malaria parasite infections [OR = 0.36, P = 0.001, 95% CI: (0.19, 0.67)]. Conclusions Timely health-seeking behaviors should be improved among imported malaria cases in Jiangsu Province, patients with a history of overseas malaria infections require faster health-seeking activities.
ABSTRACT
OBJECTIVE@#To investigate the therapeutic effect of spleen low molecular weight extracts on epileptics hydrochloride-induced leukopenia in mice and explore its mechanism.@*METHODS@#The model of leukopenia in mice was established by the injection of epirubicin hydrochloride (10 mg/kg). After the injection of chemotherapeutic drugs, leukocytopenia mice were treated with different doses of spleen low molecular weight extract, Ganoderma oral solution and recombinant granulocyte colony stimulating factor (rhG-CSF). The general survival status indicators such as body weight, coat color and athletic ability of mice in each group were recorded; the tail vein blood of mice in each group was collected and the white blood cell count in them was calculated; bone marrow of mice was taken and bone marrow smears were observed.@*RESULTS@#In the model group, the weight of the mice gradually decreased in the later period, their coat became dark and rough, and the ability to exercise decreased, while the mice in the treatment groups showed different degrees of improvement in their survival status except for the mice treated by rhG-CSF. There was no significant fluctuation in the white blood cell count of the blank control mice. After injection of epirubicin, the white blood cell count of peripheral blood in the model mice and treated mice were decreased. The white blood cell count was lower in the mice treated with high-dose low molecular weight extract and rhG-CSF than that in other experimental groups. Bone marrow smear showed that the proportion of bone marrow nucleated cells in the mice treated with the low molecular weight extract of the spleen was significantly higher than that of model mice (P<0.05).@*CONCLUSION@#The low molecular weight spleen extracts can significantly improve the hematopoietic state of mouse bone marrow, promote the proliferation of inhibited bone marrow cells, and thus has the effect of treating leukopenia in mice.
Subject(s)
Animals , Mice , Epirubicin , Granulocyte Colony-Stimulating Factor , Leukocyte Count , Leukopenia/drug therapy , Molecular Weight , Plant Extracts , Recombinant Proteins , SpleenABSTRACT
Objective@#To understand parent child communication about sex related topics in rural areas of Sichuan Province, and to provide the basis for family sex education.@*Methods@#A multi stage stratified cluster sampling was adopted to select 2 801 parents of children from 53 township kindergartens in Sichuan Province. Questionnaires were conducted to parents about sex education in family by face to face interview or self filling.@*Results@#About 41.63% of parents reported that children had questions about sex, and the rate of proper parent child communication was 57.46%. The results of binary unconditional Logistic regression analysis showed that township residence( OR=1.46, 95%CI =1.12-1.90), high school or higher educational background of mothers( OR= 1.77 , 95%CI =1.38-2.28), non-left-behind children( OR=1.32, 95%CI =1.03-1.69), supportive for parent child communication about sex related topics( OR=1.66, 95%CI =1.05-2.63), sex education at home( OR=1.60, 95%CI =1.25-2.05) were associated with a higher rate of proper parent child communication on sex( P <0.05).@*Conclusion@#In rural areas of Sichuan, proper parent child communication about sex related topics was not common. It is suggested that in rural areas, parents should enhance their awareness of the knowledge and importance of children s sex education, and improve the coping methods of children s sex-related problems so as to promote the healthy growth of children s body and mind.
ABSTRACT
ObjectiveCardiovascular disease (CVD) is the main cause of morbidity and mortality in patients with hemodialysis (HD) end-stage renal disease (ESRD). This paper analyzes and discusses the relationship between neutrophils-to-lymphocytes ratio (NLR) and heart valve calcification (CVC) in maintenance hemodialysis (MHD) patients to provide theoretical basis for the prevention and treatment of CVC.MethodsThe demographic data, relevant clinical indicators and laboratory examination results of 135 patients with MHD in the Second Hospital of Anhui Medical University were retrospectively analyzed to calculate the NLR value. Echocardiography was used to detect the incidence of CVC in the patients, and they were divided into calcification group and non-calcification group. The correlation between NLR value and CVC in MHD patients was analyzed, and the independent risk factors of CVC were discussed by using Logistic regression.ResultsAmong the 135 MHD patients, CVC was found in 59 cases (43.7%). Compared with the non-calcification group, patients in the calcification group showed significant increases in age, dialysis age, high-sensitivity c-reactive protein (HsCRP), ALP and NLR, with statistically significant differences (P5.02 (OR=17.709, P=0.046) were independent risk factors for heart valve calcification in MHD patients.ConclusionThe incidence of heart valve calcification is high in MHD patients, and NLR is an independent risk factor for it.
ABSTRACT
Objective To investigate the biologic viability and boundary range of hepatic alveolar echinococcosis (HAE) by the contrast-enhanced ultrasonography (CEUS) and acoustic radiation force impulse elastography (ARFI). Methods Totally 27 HAE patients confirmed by pathology underwent CEUS and ARFI examinations. Results Gray scale sonography of HAE showed unclear boundary, inhomogeneous, and middle hyperechoic nodules, and the maximum area was (6.08 ± 4.47) cm2 in 27 lesions. CEUS of HAE showed non-enhancement in three phases and black hole sign. Circumferential enhancement on the pe riphery of the lesion was synchronized with the liver parenchyma and showed “fast in and slow out”. The maximum area was (8.87 ± 4.83) cm2. The area of ECUS was larger than gray scale sonography in HAE (t = 2.20, P = 0.03). The mean shear wave velocities (SWVs) of the interior, the boundary range, and the surrounding liver tissues of HAE were statistically different by ARFI (F = 84.538, P < 0.001), and the interior had the highest values. Conclusions CEUS and ARFI examinations can detect the biologic viability and boundary range of migrating zone around HAE, which is valuable for guiding treatment, judging curative effect, and predicting prognosis.
ABSTRACT
<p><b>OBJECTIVE</b>The arrival of precision medicine plan brings new opportunities and challenges for patients undergoing precision diagnosis and treatment of malignant tumors. With the development of medical imaging, information on different modality imaging can be integrated and comprehensively analyzed by imaging fusion system. This review aimed to update the application of multimodality imaging fusion technology in the precise diagnosis and treatment of malignant tumors under the precision medicine plan. We introduced several multimodality imaging fusion technologies and their application to the diagnosis and treatment of malignant tumors in clinical practice.</p><p><b>DATE SOURCES</b>The data cited in this review were obtained mainly from the PubMed database from 1996 to 2016, using the keywords of "precision medicine", "fusion imaging", "multimodality", and "tumor diagnosis and treatment".</p><p><b>STUDY SELECTION</b>Original articles, clinical practice, reviews, and other relevant literatures published in English were reviewed. Papers focusing on precision medicine, fusion imaging, multimodality, and tumor diagnosis and treatment were selected. Duplicated papers were excluded.</p><p><b>RESULTS</b>Multimodality imaging fusion technology plays an important role in tumor diagnosis and treatment under the precision medicine plan, such as accurate location, qualitative diagnosis, tumor staging, treatment plan design, and real-time intraoperative monitoring. Multimodality imaging fusion systems could provide more imaging information of tumors from different dimensions and angles, thereby offing strong technical support for the implementation of precision oncology.</p><p><b>CONCLUSION</b>Under the precision medicine plan, personalized treatment of tumors is a distinct possibility. We believe that multimodality imaging fusion technology will find an increasingly wide application in clinical practice.</p>
Subject(s)
Humans , Multimodal Imaging , Methods , Neoplasms , Diagnosis , Precision Medicine , MethodsABSTRACT
Objective: To evaluate the inhibitory effect of dihydroartemisinin on neuroblastoma cell line SH-SY5Y, explore the possible mechanism of dihydroartemisinin against neuroblastoma cells. Methods: The cell viability of dihydroartemisinin treated SH-SY5Y cells was examined by MTT assay and morphology of cells was observed by using inverted microscope. Cell cycle was examined with flowcytometry assay, then cyclin D1 and caspase-3 proteins expression was detected by ELISA and western blotting assay. Results: MTT analysis results showed that cell viability significantly decreased after exposure to 0.05, 0.50, 5.00 and 50.00 μmol/L dihydroartemisinin in a dose-dependent manner, and the lower density of cells was observed in treated groups. The number of cells in sub-G1 phase was increased after treatment with different doses of dihydroartemisinin compared with the control group. The expression of cyclin D1 protein was decreased, while the expression of caspase-3 protein was increased in treated group. Conclusions: Dihydroartemisinin could inhibit the proliferation through stopping the cell cycle and inducing the apoptosis in neuroblastoma SH-SY5Y cells.
ABSTRACT
The carotid sinus baroreceptor reflex (CSR) is an important approach for regulating arterial blood pressure homeostasis instantaneously and physiologically. Activation of the central histaminergic or cholinergic systems results in CSR functional inhibitory resetting. However, it is unclear whether two systems at the nucleus tractus solitarius (NTS) level display cross interaction to regulate the CSR or not. In the present study, the left or right carotid sinus region was isolated from the systemic circulation in Sprague-Dawley rats (sinus nerve was reserved) anesthetized with pentobarbital sodium. Respective intubation was conducted into one side isolated carotid sinus and into the femoral artery for recording the intracarotid sinus pressure (ISP) and mean arterial pressure (MAP) simultaneously with pressure transducers connection in vivo. ISP was set at the level of 0 mmHg to eliminate the effect of initial internal pressure of the carotid sinus on the CSR function. To trigger CSR, the ISP was quickly elevated from 0 mmHg to 280 mmHg in a stepwise manner (40 mmHg) which was added at every step for over 4 s, and then ISP returned to 0 mmHg in similar steps. The original data of ISP and corresponding MAP were fitted to a modified logistic equation with five parameters to obtain the ISP-MAP, ISP-Gain relationship curves and the CSR characteristic parameters, which were statistically compared and analyzed separately. Under the precondition of no influence on the basic levels of the artery blood pressure, the effects and potential regulatory mechanism of preceding microinjection with different cholinoceptor antagonists, the selective cholinergic M1 receptor antagonist, i.e., pirenzepine (PRZ), the M2 receptor antagonist, i.e., methoctramine (MTR) or the N1 receptor antagonist, i.e., hexamethonium (HEX) into the NTS on the changes in function of CSR induced by intracerebroventricular injection (i.c.v.) of histamine (HA) in rats were observed. Meanwhile, the actions and possible modulatory mechanism of preceding microinjection with different histaminergic receptor antagonists, the selective histaminergic H1 receptor antagonist, i.e., chlorpheniramine (CHL) or the H2 receptor antagonist, i.e., cimetidine (CIM) into the NTS on the changes in function of CSR resulted from the i.c.v. cholinesterase inhibitor, physostigmine (PHY) were also examined in order to confirm and to analyze effects of cross interaction between central histaminergic and cholinergic systems on CSR. The main results obtained are as follows. (1) Standalone microinjection of different selective cholinergic receptor antagonists (PRZ, MTR or HEX) or different selective histaminergic receptor antagonists (CHL or CIM) into the NTS with each given dose had no effects on the CSR function and on the basic levels of the artery blood pressure, respectively (P > 0.05). (2) The pretreatment of PRZ or MTR into the NTS with each corresponding dose could attenuate CSR resetting resulted from i.c.v. HA in some degrees, which remarkably moved the posterior half range of ISP-MAP relationship curve downwards (P < 0.05), shifted the middle part of ISP-Gain relationship curve upwards (P < 0.05), and increased reflex parameters such as the MAP range and maximum gain (P < 0.05), but decreased parameters such as saturation pressure and intracarotid sinus pressure at maximum gain (P < 0.05). The catabatic effects of pretreatment with MTR into the NTS on CSR resetting induced by i.c.v. HA were more obvious than those with PRZ (P < 0.05), but pretreatment of HEX with given dose into the NTS had no effects on CSR resetting induced by i.c.v. HA (P > 0.05). (3) The effects of pretreatment of CHL or CIM into the NTS with each corresponding dose on CSR resetting made by i.c.v. PHY were similar to those of pretreatment of PRZ or MTR into the NTS on CSR resetting resulted from i.c.v. HA, and the decreasing effects of pretreatment with CHL into the NTS on CSR resetting induced by i.c.v. PHY were more remarkable than those with CIM (P < 0.05). These findings suggest that CSR resetting resulted from either HA or PHY into the lateral ventricle may partly involve the descending histaminergic or cholinergic pathway from the hypothalamus to NTS, which might evoke a cross activation of the cholinergic system in the NTS, via cholinergic M1 and M2 receptors mediation, especially the M2 receptors showing actions, or trigger another cross activation of the histaminergic system in the NTS, by histaminergic H1 and H2 receptors mediation, especially the H1 receptors displaying effects.
Subject(s)
Animals , Rats , Baroreflex , Carotid Sinus , Physiology , Chlorpheniramine , Pharmacology , Cholinergic Antagonists , Pharmacology , Cimetidine , Pharmacology , Histamine , Pharmacology , Pressoreceptors , Physiology , Rats, Sprague-Dawley , Solitary Nucleus , PhysiologyABSTRACT
Protein disulfide isomerase-related protein A (PRPA) was highly expressed (about 34%) in Escherichia coli by inserting the whole PRPA cDNA into the vector pET23b. After expression, the purified protein was acquired through ammonium fractional precipitation and Bio-Rex 70 chromatography. PRPA shows low disulfide isomerase activity (only about 1/250 of that of hPDI), decreases the reactivation yield of denatured and reduced lysozyme either in redox and non-redox Hepes buffer or redox PBS buffer and facilitates the aggregation of denatured and reduced lysozyme. Fluorescence spectra of PRPA indicate that PRPA has more hydrophobic groups at surface than that of hPDI, and which can be used to explain why PRPA has anti-chaperone activity during the refolding of denatured and reduced lysozyme.
Subject(s)
Cloning, Molecular , Fungal Proteins , Chemistry , Genetics , Muramidase , Chemistry , Plasmids , Protein Folding , Recombinant Proteins , Spectrometry, FluorescenceABSTRACT
The mechanism of oxidative refolding of proteins was elucidated in more detail from the intensive and extensive studies in the past decades. 1. Most of the proteins examined so far proceed oxidative refolding via multiple pathways rather than a single and specific pathway. This is consistent with the folding energy landscape theory. 2. It is the native interactions rather than the non-native interactions that direct the folding process. This is not necessarily incompatible with the importance of the non-native disulfide intermediates in the bovine pancreatic trypsin inhibitor (BPTI) pathway, which are just a chemical necessity in the intramolecular arrangement to facilitate native disulfide formation. 3. Based on the BPTI refolding it was suggested that disulfide bonds have a stabilizing effect on the native state without determining either the folding pathway or the final three-dimensional structure of the protein. This point of view is not applicable to other proteins. Studies on the refolding of prochymosin unequivocally demonstrated that the formation of native disulfides is the prerequisite to the recovery of the native conformation. It is more likely that the interdependence between the native disulfide formation and the formation of native structure is a general rule. 4. At the early stage of oxidative refolding disulfide formation is essentially a random process, with the progress of refolding further disulfide formation is increasingly dependent on the conformations of the intermediates. Enhancing the renaturation yield of recombinant proteins is a major challenge in biotechnology. In addition to aggregation, the formation of species with mispaired disulfide bonds is a leading cause of decreased yield. Progress in understanding the mechanism of oxidative refolding has provided insight into how to solve this problem. As described above, at the later stage of refolding disulfide formation depends on the conformations of intermediates. The intermediates with native-like and flexible structure favourable for native disulfide formation and correct refolding are productive intermediates, while the unproductive intermediates tend to adopt stable conformations, which render the thiol groups and disulfide bond(s) inaccessible and further folding unfavourable energetically. Therefore, the principle to enhance the renaturation yield of disulfide-containing proteins is to cause the productive intermediates to predominate by destabilizing the unproductive intermediates. To approach this, alkaline pH, low temperature, labilizing agents, protein disulfide isomerase and its analogues and alteration of primary structure have been proved useful to adjusting the structure of the unproductive intermediates so as to facilitate thiol/disulfide interchange and in turn the native disulfide formation. The prospects for the oxidative refolding of proteins both in basic and applied researches are discussed in this review article.